Scientists Discover a Depression Subtype Linked to the Body's Internal Clock

Could your body's internal clock explain why some forms of depression do not respond well to conventional antidepressants? A new study has identified a potential subtype of depression called "circadian depression," affecting nearly one-quarter of individuals with severe, recurrent or persistent depression.

Published in the British Journal of Psychiatry, the study conducted by researchers at the University of Sydney examined clinical and genetic data from more than 10,000 Australians participating in the Australian Genetics of Depression Study.

Circadian depression is associated with disturbances in the body's 24-hour biological clock, which regulates sleep, wakefulness and other physiological processes.

Researchers identified 2,604 participants, representing approximately 25% of the study population, with characteristics consistent with circadian depression.

Common features included seasonal patterns of depressive symptoms, prolonged sleep during depressive episodes, persistent tiredness upon waking and a preference for staying awake late at night.

The findings also revealed that individuals with circadian depression were more likely to experience depressive symptoms earlier in life and report greater illness severity, including increased suicidal thoughts and symptoms of mania.

Genetic analyses additionally identified higher susceptibility to inflammatory and cardiovascular conditions and neurodevelopmental disorders, including attention-deficit/hyperactivity disorder (ADHD).

Importantly, participants with circadian depression showed poorer responses and more side effects with commonly prescribed antidepressants, including selective serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors (SNRIs).

Researchers suggested that treatments targeting circadian rhythms, such as light therapy, melatonin and melatonin-targeting antidepressants, may be more suitable for some individuals with this presentation.

However, these findings do not establish that circadian-focused treatments are superior for every patient, and treatment decisions require individual clinical assessment. Researchers believe that identifying circadian-related symptoms earlier could help clinicians personalise treatment strategies.

REFERENCE: Dr Emiliana Tonini, et al.; Clinical and genetic correlates of a circadian subtype of depression in the Australian Genetics of Depression Study; British Journal of Psychiatry; DOI: 10.1192/bjp.2026.10798